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ESTRO 36 2017
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adjusted and thresholded to create a binary 3D vessel map
(VM). Hoechst-negative vessels were excluded from the
VM. These VMs were used to simulate 3D oxygen
distributions based on a Michaelis-Menten relation. An
average input function (AIF) was determined by fitting
activities in the left ventricles over 4 mice to derive mean
parameters. Based on oxygen distribution and AIF, FMISO
retention was simulated on the same VMs. FMISO-positive
regions of 3x3mm2 in the tumor center in 5 random
sections were compared against manually contoured
pimo-positive regions to validate the simulation by
determining hypoxic fraction (HF) and overlap ratio.
Necrosis was excluded based on H/E staining on the same
sections. To compare 3D and 2D simulations, the
simulations and analysis were repeated in 2D. Parameters
for all simulations were set to commonly used values
(Mönnich et al., 2011).
Results
Differences in experimental and 3D-simulated hypoxic
fractions (HF) were not significant, while differences
between experimental and 2D-simulated HF was
significantly different for Tumor 2 (p=0.02, cf. Table).
3D simulations matched much better with pimo
distribution than 2D simulations only. The true-positive
rate was increased about 0.2 for both tumors, the true-
negative rate by about 0.08 for 3D simulations when
compared to 2D. 56% of 3D-simulated FMISO-positive
voxels were located within pimo-positive areas, while
another 14% were located within 50µm distance, as to 37%
and 8% for 2D, respectively (cf Table, Figure).
Conclusion
When performing hypoxia tracer simulations on actual
VMs, 3D models accounting for out-of-plane diffusion must
be used to obtain realistic results. In a 3D vascular model,
spatial tracer distributions similar to those observed
in
vivo
can be simulated. Hence, 3D FMISO simulation on
realistic VMs can help to optimize clinical imaging
protocols and image analysis tools.
PO-0888 Response monitoring by 18FDG-PET in locally
advanced NSCLC treated with concurrent
chemoradiotherapy
J.N.A. Van Diessen
1
, M. La Fontaine
2
, M. Van den
Heuvel
3
, W. Vogel
4
, J.S.A. Belderbos
1
, J.J. Sonke
2
1
Netherlands Cancer Institute Antoni van Leeuwenhoek
Hospital, Radiation Oncology, Amsterdam, The
Netherlands
2
Netherlands Cancer Institute Antoni van Leeuwenhoek
Hospital, Academic Physics, Amsterdam, The
Netherlands
3
Netherlands Cancer Institute Antoni van Leeuwenhoek
Hospital, Pulmonology, Amsterdam, The Netherlands
4
Netherlands Cancer Institute Antoni van Leeuwenhoek
Hospital, Nuclear Medicine, Amsterdam, The
Netherlands
Purpose or Objective
The randomized phase 2 Raditux-trial (NTR2230) in locally
advanced non-small cell lung cancer (NSCLC),
investigating the additional benefit of Cetuximab to
concurrent chemoradiotherapy (CCRT) did not show
improved survival but revealed a remarkable 5-year
overall survival (OS) of 37.3% [1]. Patients were staged
with
18
FDG-PET-scans before and 4 weeks after CCRT. The
purpose of this study was to investigate whether PET
metrics have prognostic value in relation to local,
regional, and distant failure.
Material and Methods
In the Raditux-trial, 102 stage IIIA-B NSCLC patients were
included. CCRT consisted of 66 Gy in 24 fractions (using
IMRT) combined with daily low dose Cisplatin. A subgroup
of the patients had a repeat
18
FDG-PET-scan for response
evaluation of the primary tumor and lymph nodes after a
median of 4.2 weeks (range, 1.6-10.1). Twenty patients
underwent additional surgery and were excluded. Ten
patients were excluded due to technical reasons. The pre-
and post-treatment
18
FDG-PET-scans from the remaining
42 patients were anatomically registered with the
planning CT-scan. The following pre-and post-treatment
PET metrics were calculated of the primary tumor (PT) as
well as the combined lymph nodes (LNs): SUV
max
, total
lesion glycolysis (TLG) and metabolic tumor volume (MTV).
The response ratio between the pre- and post-treatment
values was also calculated. These parameters were tested
as prognostic factors using the Kaplan-Meier method and
Cox regression analysis for univariate and multivariate
analyses.
Results
Forty-two patients were evaluated for the prognostic
value of the PET metrics. The median follow-up and OS
was 32 and 33 months, respectively. Median GTV of the PT
and the LNs was 80 cc (range, 2-439) and 27 cc (range, 2-
195). The SUV
max
of both PT and LNs decreased
significantly as well as TLG of the PT and MTV of the LNs
(p≤0.001). The post-treatment and the response ratio of
the SUV
max
of the LNs was correlated significantly with
regional failure (p=0.009; p=0.009) (Table 1). The
response ratio of the SUV
max
of the LNs was also
significantly correlated with OS (p=0.014). No parameters
corresponded with local and distant failure.
Table 1
The P-values and HR of the PET metrics of the primary
tumor (PT) related to local failure and combined lymph
nodes (LNs) related to regional failure of the pre- and
post-treatment
18
FDG-PET-scan as well as the response
ratio.